The rapid increase in the incidence of gram-positive infections—including those caused by resistant bacteria—has sparked renewed interest in the development of novel classes of antibiotics. A class of compounds which have shown potential as useful antibiotics includes the A-21978C lipopeptides described in, for example, United States Patents RE 32,333; RE 32,455; RE 32,311; RE 32,310; U.S. Pat. Nos. 4,482,487; 4,537,717; and 5,912,226 and U.S. patent applications Ser. Nos. 09/738,742; 09/737,908; and 09/739,535 filed Dec. 15, 2000.
Daptomycin, a member of the A-21978C lipopeptides, is described by Baltz in Biotechnology of Antibiotics, 2nd Ed., ed. W. R. Strohl (New York: Marcel Dekker, Inc.), 1997, pp. 415–435. Daptomycin, also referred to as LY 146032, has an n-decanoyl side chain linked to the N-terminal tryptophan of a three-amino acid chain, which is linked to a cyclic 10-amino acid peptide. The reported structure (see, e.g., U.S. Pat. No. 4,537,717) of daptomycin is shown below:

Daptomycin has potent bactericidal activity in vitro and in vivo against clinically relevant gram-positive bacteria that cause serious and life-threatening diseases. These bacteria include resistant pathogens, such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide intermediate susceptible Staphylococcus aureus (GISA), coagulase-negative staphylococci (CNS), and penicillin-resistant Streptococcus pneumoniae (PRSP), for which there are few therapeutic alternatives. See, e.g., Tally et al., 1999, Exp. Opin. Invest. Drugs 8:1223–1238.
Despite the promise that existing antibacterial agents have shown, the need for novel antibiotics continues. Many pathogens have been repeatedly exposed to commonly-used antibiotics. This exposure has led to the selection of variant antibacterial strains resistant to a broad spectrum of antibiotics. The loss of potency and effectiveness of an antibiotic caused by resistant mechanisms renders the antibiotic ineffective and consequently can lead to some life-threatening infections that are virtually untreatable. As new antibiotics come to market pathogens may develop resistance or intermediate resistance to these new drugs, effectively creating a need for a stream of new antibacterial agents to combat these emerging strains. In addition compounds that exhibit bactericidal activity offer advantages over present bacteriostatic compounds. Thus, novel synthetic antibacterial agents would be expected to be useful to treat not only “natural” pathogens, but also intermediate drug resistant and drug resistant pathogens because the pathogen has never been exposed to the novel antibacterial agent. New antibacterial agents may exhibit differential effectiveness against different types of pathogens.
Known processes for the production of daptomycin involve the fermentation of Streptomyces roseosporus resulting in the formation of daptomycin as a single stereoisomer (see, for example, United States Patents RE 32,333; RE 32,455; RE 32,311; U.S. Pat. Nos. 4,482,487; 4,537,717; 4,800,157, 4,874,843; 4,885,243 and 5,912,226). Stereoisomers of daptomycin and processes for the production of these stereoisomers have not been reported. New processes that allow for the preparation of a variety of daptomycin stereoisomeric compounds would therefore be advantageous.